The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; 18 of the 59 sources its claims cite were checked for support.
Nonviral delivery of self-amplifying RNA vaccines
Open accessAbstract
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Nonviral delivery of a 9-kb self-amplifying RNA encapsulated in lipid nanoparticles (LNP/RNA) increased reporter gene expression and immunogenicity compared with unformulated RNA. In mice and cotton rats, LNP/RNA elicited potent RSV-F-specific humoral and cellular responses and protection from RSV challenge comparable to viral replicon particle delivery.
Key findings
- LNP encapsulation protected self-amplifying RNA from RNase degradation and improved in vivo expression: 0.1 μg LNP/RNA increased serum SEAP over 1 μg naked RNA and reduced animal-to-animal variability.
- After two intramuscular immunizations, 0.1 μg LNP/RNA encoding RSV-F elicited F-specific IgG GMT 26,170 versus 2,292 for 1 μg naked RNA; 1 μg LNP/RNA was equivalent to 1 × 10⁶ IU VRPs (GMT 10,478), and seroconversion occurred after a single LNP/RNA dose as low as 0.01 μg RNA.
- In cotton rats, LNP/RNA boosted F-specific IgG approximately 8-fold (GMT 4,355 vs. 526) and RSV neutralization titers 10-fold (GMT 1,493 vs. 154) relative to the same dose of naked RNA, equivalent to 5 × 10⁶ IU VRPs (GMTs 5,861 and 1,690); all self-amplifying RNA vaccines reduced lung viral load >1,000-fold versus controls after intranasal RSV challenge.
- LNP/RNA elicited slightly elevated F-specific IgG2a relative to IgG1 and potent antigen-specific IFN-γ-producing CD4⁺ and CD8⁺ T cell responses; functional immune responses against HIV antigens were also observed (Fig. S5).
Methods
- Preclinical vaccine study using a self-amplifying RNA based on an alphavirus genome, produced by T7 RNA polymerase transcription from linear pDNA and encapsulated in lipid nanoparticles via an ethanol dilution process using DLinDMA, DSPC, cholesterol, and PEG-DMG 2000.
- Female BALB/c mice (8–10 wk, ~20 g) and female cotton rats were immunized intramuscularly on days 0 and 21; cotton rats were challenged intranasally with 1 × 10⁵ pfu RSV 4 wk after the final immunization.
- Main analyses included serum SEAP and luciferase bioluminescence, RSV-F-specific IgG/IgG1/IgG2a ELISA, RSV neutralization titers, T cell cytokine flow cytometry, and lung viral load; statistics used one-way ANOVA or Kruskal-Wallis with Dunn’s posttest at 95% confidence.
Limitations
- Stated: immunogenicity at submilligram doses in larger species “remains to be directly tested”; the mechanism of action is not fully elucidated, and studies are underway to identify transfected cells and explain why LNP delivery gives longer expression than VRP delivery.
- Stated: production of larger (~9 kb) self-amplifying RNA adds challenges, though the authors call them “not insurmountable.”
- Evident from the text: all efficacy and challenge data are from mice and cotton rats, with no human or nonhuman primate data reported for this LNP/RNA vaccine.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
31 Own result · 16 No full text of the sources · 14 Own interpretation · 7 Supported · 6 Partly supported · 5 No basis given · 2 Supported so far · 1 Own method · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, naked RNA vaccines suffer from limited potency, in part due to RNA instability in vivo, related to the presence of degradative enzymes in tissues (15).”
What the sources say
- Supportedcites [15] source
The Background states that ubiquitous ribonucleases rapidly degrade mRNA and that this instability limits the efficacy of mRNA-based therapies. The Conclusion applies that concern to mRNA vaccination, proposing protection from RNases to improve vaccine efficacy. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, for infant RSV vaccine development, safety considerations favor replicating (or selfamplifying) vaccine candidates over subunit approaches (33).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
What the sources say
- Supportedcites [33] source
The “Subunit proteins” section says subunit vaccines face significant regulatory hurdles in seronegative infants and raises theoretical concerns about vaccine-enhanced disease relative to live-attenuated viruses or gene-based vectors. This supports the claim as a statement about safety considerations, not as proof that every replicating candidate is safe. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similarly, EP-mediated delivery of pDNA has been shown to be broadly effective (26) and thus was used as the benchmark for pDNA delivery.”
What the sources say
- Supportedcites [26] source
The “Electroporation Enhanced DNA Vaccine Delivery” section reports a 100–1000-fold enhancement in plasmid delivery and gene expression compared with DNA delivery without EP. The “Translating In vivo Expression to Immunogenicity and Efficacy” section describes enhanced responses across numerous vaccine candidates and animal disease models. Together, these support the broad effectiveness attributed to EP-mediated pDNA delivery; page numbers were not supplied. (LLM, conf=0.91)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“VRPs have been shown to be potent in nonhuman primates and humans at a 100-fold higher dose (1 × 10 8 IU) (22,25), and thus we anticipate that this unique RNA vaccine will be immunogenic at submilligram doses in larger species, but this remains to be directly tested.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
Materials and Methods reports a VRP dose of 1 × 10^8 IU in rhesus macaques, and the Results and Discussion report immune responses and protection with a VRP-prime/Env-protein-boost regimen. The copy does not establish potency in humans or that this dose was 100-fold higher than a comparison dose; it also reports that VRP alone did not protect the macaques. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [25] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The current costs of clinical manufacturing of pDNA are on the order of $50-100 per milligram (1-10 g scale) (26).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Supportedcites [26] source
The “Prospects for Clinical Efficacy and Product Development Success” section states that current small-scale cGMP DNA manufacturing costs are approximately $50–100 per milligram at a 1–10 g manufacturing scale. This matches the cited claim about clinical pDNA manufacturing costs. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the naked control RNA was degraded by RNase A (Fig. 1C, lane 3 compared with lane 2).”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Importantly, the immunogenicity and protective efficacy generated by 1 μg LNP/RNA was equivalent to the responses elicited by the VRP delivery technology.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 38
- Probably not a substantial claim. 9
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although plasmid DNA (pDNA) vaccines have proven to be a flexible platform and are broadly effective in small animal models, they have generally lacked potency in human clinical trials (2).”
What the sources say
- Supportedcites [2] source
The Preclinical studies section reports protective immunity against a broad range of pathogens in small-animal studies and describes applications beyond infectious disease. The DNA vaccine platform: room for improvement section says responses in humans have been significantly weaker than in mice, and Initial DNA vaccine studies in humans says greater potency is needed. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, with increasing life expectancy in high-income countries and newly emerging infections and poverty in low-income countries, new technologies will be required to address changing vaccine needs (1).”
What the sources say
- Supportedcites [1] source
The Main section identifies an aging society, emerging infections, and poverty in low-income countries as changing health needs. It also says emerging infections require appropriate technologies and that research into novel vaccine technologies remains a priority. No page numbers are available in our copy. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“VRPs are potent vaccines in mice (10,11), nonhuman primates (11,22), and humans (25).”
What the sources say
- Supportedcites [10] source
The Discussion reports potent vaccine responses in mice, and the Abstract states that VEE replicon particles induced potent, protective immune responses in primates. In the citing sentence, this source is cited for mice and nonhuman primates; the human claim is assigned to citation 25, not this paper. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [11] source
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports complete protection of rhesus macaques given an intramuscular VRP prime plus Env-protein boost, supporting the nonhuman-primate portion attributed to this source. It also says none of the macaques given VRP alone were protected, so the unqualified description of VRPs as potent vaccines overstates this study. The separate mice and humans citations are not being judged here. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [25] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“There are limited published data on the in vivo delivery of self-amplifying RNA using nonviral delivery strategies (3,14,18), and none has taken advantage of the recently developed, clinically suitable delivery systems for siRNA (19,20).”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [14] source
This paper is cited for the first clause: examples of in vivo, nonviral delivery of self-amplifying RNA. The Discussion describes delivery of naked Semliki Forest virus RNA replicons and reports immune responses after intradermal delivery with electroporation. The separate claim about siRNA delivery systems is attached to other citations, not this paper. (LLM, conf=0.90)
- Not matchedcites [18]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [19] source
- Supportedcites [20] source
The Main section (page unavailable) describes synthetic, nonviral siRNA delivery systems that have worked in vivo and says several clinical trials use delivery agents. This supports the cited description of clinically promising siRNA delivery systems; the statement that self-amplifying RNA studies had not used them is the citing authors’ comparison, not a finding attributed to this source. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Injection of naked mRNA or self-amplifying RNA in vivo induces gene expression and generates immune responses (4, 11-13), with self-amplifying RNA being more efficient for gene expression in situ (13,14).”
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [11] source
- Not checked — no full text of the sourcecites [12] source
- Partly supportedcites [13] sourceExperimental — accuracy not yet measured
The in vivo gene-expression results report that injected replicative mRNA produced substantially more luciferase than non-replicative mRNA in muscle. The Discussion reports an immune response from prior CEA mRNA injections, but this study did not establish that its self-amplifying RNA generated an immune response; it discusses that possibility as a hypothesis (page not provided). (LLM, conf=0.87)
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Results section ('Relative expression levels and cellular immune response'; page unavailable) reports in vivo gene expression from both mRNA and replicon RNA, with lower, shorter-lived expression from mRNA. Replicon RNA elicited immune responses, but naked mRNA produced no detectable specific immune response in this study's single-injection experiments. The Introduction does report immune responses to mRNA vaccination in other studies, so the broad claim is supported only with that qualification. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
Every source the paper cites for this claim was checked and supports it.
In the paper
“The F protein of RSV is a conserved target of neutralizing antibodies and a promising antigen for RSV vaccine development (29).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
What the sources say
- Supportedcites [29] source
The introductory passage following the Abstract explicitly calls RSV F “a conserved target of neutralizing antibodies” and “a promising antigen for RSV candidate vaccines.” The Discussion further reports that an engineered F antigen elicited high neutralizing antibody titers and protected cotton rats from RSV challenge. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The neutralization titers elicited by LNP/RNA are above the titer of 380 that correlates with protection in cotton rats (30) and similar to passively acquired serum neutralizing titers that correlate with protection of human infants from severe RSV disease (31,32).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Currently there is no vaccine for RSV and, because of a history of disease enhancement upon natural infection after immunization with an RSV vaccine candidate that elicited T H 2-biased (and non-neutralizing) RSV-specific immune responses in RSV-naive infants, elicitation of a non-T H 2-biased RSV-specific response is considered an essential attribute for infant RSV vaccine candidates (33).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Partly supportedcites [33] sourceExperimental — accuracy not yet measured
The Major hurdles section says adequate RSV vaccine options were unavailable and describes enhanced disease in infants after the formalin-inactivated vaccine. The Vaccine-enhanced disease section reports poor neutralizing antibody responses in those children, and the Role of T cells in vaccine-enhanced illness section recommends avoiding Th2 responses in RSV vaccines. However, it identifies clear Th2 induction in immunized animal models, not as a directly established response in the infants; their lung eosinophilia is cited as a reason for concern. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The shorter duration of expression in situ after RNA immunization compared with pDNA may be related to the induction of apoptosis of the transfected cell, which could occur during RNA amplification, leading to transient gene expression (12,13).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [12] source
- Partly supportedcites [13] sourceExperimental — accuracy not yet measured
The in vivo results report that replicative mRNA expression returned to baseline within 28 days, while plasmid DNA expression remained above baseline (Augmented gene expression in vivo). The Discussion proposes host-cell protein-synthesis inhibition and resulting cytopathogenicity as one possible explanation for the decline in mRNA-directed expression. It does not specifically identify apoptosis or establish that it occurs during RNA amplification. (LLM, conf=0.85)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recently, there has been an exponential growth in the development of clinically suitable nonviral delivery systems for siRNA (19,20); we have taken advantage of these innovations to develop the LNP/RNA formulation and have now embarked on a more extensive evaluation of other nonviral delivery systems.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [19] source
- Partly supportedcites [20] sourceExperimental — accuracy not yet measured
The Main section describes advances in synthetic nonviral siRNA carriers and reports that some delivery agents are being used in clinical trials. It does not establish exponential growth, and it says safe, effective delivery remains a barrier rather than characterizing these systems generally as clinically suitable. Page numbers were not provided in our copy. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The same self-amplifying RNA, when delivered using a VRP (1 × 10 6 IU), produced twice the bioluminescence at day 3 compared with LNP/RNA, but expression decayed much more rapidly and reached background levels by day 28 (Fig. 2B).”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EP delivery of pDNA (at a high dose of 20 μg) elicited anti-F IgG titers (GMTs of 6,712) on average 3.9-fold less than those elicited by 0.1 μg of LNP/RNA, although not statistically different.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, mice administered a pDNA-encoding luciferase (10 μg) delivered using EP in situ displayed the highest measurable bioluminescence at all time points tested, and this level remained high for at least 63 d (Fig. 2D).”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Encapsulation of a 10-fold lower dose of RNA (0.1 μg) in LNPs increased the serum SEAP concentration and reduced the variability between animals.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Six days after intramuscular (i.m.) injection of 1 μg naked self-amplifying RNA encoding secreted alkaline phosphatase (SEAP), gene expression, as determined by serum SEAP concentration, was measurable but highly variable (Fig. 1D).”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This contrasted with what was observed for naked RNA, which required two vaccinations and microgram doses of RNA.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The LNP/RNA was statistically superior to naked RNA and equivalent to the 5 ×10 6 IU of VRPs [GMTs 5,861 (F-specific IgG) and 1,690 (neutralization)].”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Addition of empty LNPs (without RNA) to naked RNA (0.1 μg) decreased the serum SEAP concentration relative to LNP-encapsulated RNA, indicating that RNA encapsulation was necessary for efficient RNA delivery and reporter gene expression.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A recombinant F protein subunit vaccine formulated with alum was shown to be the most potent vaccine for induction of total and protective antibody responses.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Bioluminescence intensity induced by LNP/RNA was substantially greater than naked RNA, pDNA, and pDNA launched RNA, and was comparable to the bioluminescence produced by 1 × 10 6 infectious units (IU) of VRPs.”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Agarose gel electrophoresis showed that RNA integrity was maintained during formulation (Fig. 1C, lane 4) and that the LNPs protected the RNA from degradation by RNase A (Fig. 1C, lane 5).”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In an extended study (Fig. 2 B-D), mice injected with LNP/RNA (1 μg) showed measurable bioluminescence that was already high on day 3, peaked on day 7, and decreased to background by day 63 (Fig. 2C).”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The potency of this unique LNP/RNA vaccine in mice and cotton rats was comparable to a single-cycle alphavirus vector (VRP, 1 × 10 6 IU) at a reasonable dose of RNA (1 μg) and was generally comparable to pDNA delivered using EP at higher doses.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“All self-amplifying RNA vaccines provided protection from a nasal RSV challenge, reducing the lung viral load >1,000-fold compared with control animals (Fig. 5C) and these data are in agreement with previous reports for naked RNA (12).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
What the sources say
- Not checked — no full text of the sourcecites [12] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The LNP/RNA formulation boosted F-specific IgG titers approximately 8-fold (GMTs 4,355) and neutralization titers 10-fold (GMTs 1,493) relative to the same dose of naked RNA [GMTs of 526 (F-specific IgG) and 154 (neutralization)].”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“An ethanol dilution process (28) was used to produce small uniform lipid particles with a high RNA encapsulation efficiency.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
What the sources say
- Not checked — no full text of the sourcecites [28] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number-weighted mean diameters ranged from 79 to 121 nm and Z-average diameters from 130 to 164 nm with a polydispersity index from 0.09 to 0.14.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ratio of F-specific IgG titer to RSV neutralization titer (Table S2) is low for the LNP/ RNA vaccine relative to the RSV-F subunit adsorbed on alum; thus it may be particularly suitable for development into a safe and effective infant RSV vaccine candidate.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The LNP/RNA provides this benefit (Fig. 4) in addition to strong cellular immune responses.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“(iv) the generation of a humoral and cellular immune responses (both CD4 and CD8).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Facilitated delivery of RNA, either by VRPs or LNPs, resulted in higher levels of reporter gene expression (SEAP and luciferase) than naked RNA delivery and considerably lower variability of expression between animals.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, many of the obstacles to mRNA vaccine development have been surmounted, and recently there has been a revival in the use of nonamplifying mRNA vaccines for cancer (6), allergy (7), and gene therapy (8).”
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Naturally transient and cytosolically active mRNA can now be produced at sufficient quantity and quality for human clinical trials (6) and is seen by many (9) as a safer and more potent alternative to pDNA for vaccination.”
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Viral vector-based technologies are generally regarded as the most efficient means to deliver nucleic acids into cells, but their utility can be restricted by preexisting or vaccine-induced antivector immunity that can decrease vaccine potency (12).”
What the sources say
- Not checked — no full text of the sourcecites [12] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Recombinant viral vector technologies have the advantage of efficient delivery of the nucleic acid payload, but their utility is often hampered by antivector immunity, production limitations, and safety concerns (3,4).”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Not checked — no full text of the sourcecites [4]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Various RNA vaccines have been evaluated in human clinical trials, including naked and formulated non-amplifying mRNA (37-39) and self-amplifying RNA packaged in VRPs (25).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“RNA vaccines avoid this rate-limiting step by using cytoplasmic amplification and expression, resulting in more efficient transfection of different cell types, including quiescent or slowly proliferating cells, such as vascular endothelia or myocytes.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, the LNP formulation markedly enhances the potency of the self-amplifying RNA, thereby generating a robust and potentially generic vaccine technology.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Image acquisition times were kept constant as bioluminescence was measured with a cooled CCD camera.”
§ Nonviral delivery of self-amplifying RNA vaccines > RNA Synthesis.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Those studies showed RNA vaccines to be well tolerated and immunogenic.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, because the replication cycle of the self-amplifying RNA is strictly cytoplasmic, the need for codon modification is diminished, and the risks of splicing and destruction of the transcript are avoided.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For an LNP/RNA vaccine, this sequestration might result in antigen production and/or stimulation of innate immune pathways within these immune cells.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(ii) elimination of theoretical risks of generating infectious virus through recombination during production”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The LNP delivery system may achieve these effects by a combination of increased transfection efficiency and protection of the RNA from enzymatic degradation at the site of injection.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
There is still no commercial product for human use for nucleic acid vaccines despite more than two decades of research and development.
“Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use.”
The paper relies on this without support.
mRNA-based vaccines must match the potency of viral vectors at doses of RNA that are not cost prohibitive to be commercially competitive as a platform technology.
“However, to be commercially competitive as a platform technology, mRNA-based vaccines must match the potency of viral vectors at doses of RNA that are not cost prohibitive.”
The paper relies on this without support.
The major limitation for delivery of pDNA is the nuclear barrier, and transport across the nuclear membrane is particularly inefficient in nondividing cells such as mature myocytes.
“The major limitation for delivery of pDNA is thought to be the nuclear barrier, and transport across the nuclear membrane seems to be particularly inefficient in nondividing cells, such as mature myocytes.”
The paper relies on this without support.
The immunogenicity and protection observed in mice and cotton rats are predictive of efficacy in humans.
“Thus, this technology has potential as a platform to address multiple disease targets.”
The paper relies on this without support.
The SAM vaccine platform can be applied to multiple disease targets.
“Thus, this technology has potential as a platform to address multiple disease targets.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Studies with self-amplifying mRNA vaccines investigated the effect of different formulations such as lipid-nanoparticles (LNP)10 or cationic nanoemulsion (CNE)11 on the immunogenicity of mRNA vaccines. Self-amplifying vaccines benefited from formulation with LNP or CNE and were able to induce protective antibody titers.”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [10]
In the citing paper
“Decades later, Geall and colleagues were the first to use LNP to encapsulate a saRNA chimera composed of the Venezuelan equine encephalitis virus (VEEV) and Sindbis virus (SINV) replicons into a vaccine which was used to immunize mice, and immunogenicity was significantly improved compared with unencapsulated group.199”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [199]
In the citing paper
“Based on the potential toxicity of liposomes in clinical application,25,26 the success of the first approved small interfering RNA-lipid nanoparticle (LNP) therapeutic27 and mRNA COVID-19 vaccines originates only from their delivery using ionizable lipid-containing LNPs,28, 29, 30”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [30]
In the citing paper
“In preclinical studies, mRNA vaccines encoding either the native RSV F protein or the stabilized prefusion conformation were successfully delivered using cationic nanoemulsions109 and LNPs179,180 without any observed instances of VAED.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [180]
Citations
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BackgroundDNA vaccines: ready for prime time?
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Induction of virus‐specific cytotoxic T lymphocytes in vivo by liposome‐entrapped mRNA
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Vaccines for the twenty-first century society
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Cited by
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Items 501–600 of 673
Situación actual y perspectivas de futuro de las vacunas frente al virus respiratorio sincitial
Reina, J., & de Herrero, E. G. (2023) · Vacunas · doi:10.1016/j.vacun.2022.12.005 · Cited by 5
Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer
Xu, Y., Huang, S.-W., Ding, H., & Ma, Y. (2023) · Chinese Physics B · doi:10.1088/1674-1056/ad1178 · Cited by 5
Salehi-Shadkami, H., Sedghi, M., Tavoosi, S., Alimohammadi, M., Alimohammadi, R., Barkhordar, M., Mofayezi, A., Modaresi, M. S., Vaezi, M., Dehghanizadeh, S., et al. (2025) · Current Research in Translational Medicine · doi:10.1016/j.retram.2025.103563 · Cited by 6
Vaccine Design in the 21st Century
Bottomley, M. J., Rappuoli, R., & Finco, O. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802174-3.00003-5 · Cited by 5
Self-citationDendrimers: A Novel Nanomaterial
Pramanik, D., Kanchi, S., Ayappa, K. G., & Maiti, P. K. (2021) · Springer series in materials science · doi:10.1007/978-3-030-18778-1_19 · Cited by 6
Messenger ribonucleic acid vaccines for severe acute respiratory syndrome coronavirus-2 – a review
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“Initially this delivery system was studied for small interfering RNA molecules, however it has subsequently been shown to be a successful and well tolerated method for both non-replicating mRNA and SAM delivery.(26,27) Several studies have evaluated different routes of delivery of mRNA vaccines including intravenous,…”
MethodIn vivo assessment of triazine lipid nanoparticles as transfection agents for plasmid DNA
Nardo, D., Pitts, M. G., Kaur, R., & Venditto, V. J. (2022) · Biomaterials Science · doi:10.1039/d2bm01289h · Cited by 5
González-Meléndez, A., Báez-Negrón, L., Ríos-Rivera, R., et al. (2023) · Lupus · doi:10.1177/09612033231151898 · Cited by 5
Nanoscale Vaccines: Design, Delivery, and Applications
Omidi, Y., Pourseif, M. M., Omidian, H., & Barar, J. (2021) · Wiley eBooks · doi:10.1002/9783527832095.ch14 · Cited by 6
Unraveling the potential: mRNA therapeutics in oncology
Gawalski, K., Przybyszewska, W., Hunia, J., Gawalska, A., & Rymarz, A. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1643444 · Cited by 6
“It was essential to develop lipid nanoparticles (LNPs) (24), which are one of the most employed ways to introduce mRNA into the human body in clinical trials today.”
Li, M., Guo, P., Song, H., Chen, C., Zhou, H., & Pan, T. (2025) · Animal Diseases · doi:10.1186/s44149-025-00187-6 · Cited by 6
“In addition, delivery systems such as lipid nanoparticles (LNPs) (Geall et al. 2012; Ulmer et al. 2015) and cationic nanoe-mulsions (CNEs) (Brito et al. 2014) are frequently used to protect mRNAs and promote their cellular uptake.”
RNA vaccines for cancer: revolutionizing immunization strategies
Huang, D., Zhang, J., Zeng, X., Zhang, Y., & Song, E. (2025) · Trends in cancer · doi:10.1016/j.trecan.2025.09.003 · Cited by 4
Health Technology Assessment of mRNA Vaccines: Clinical, Economic, and Public Health Implications
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“6 Replicons are of great interest for RNA vaccination, as they have the potential to enable much lower total doses of RNA to be used, 9–12 and concomitantly, lower doses of lipid delivery vehicle, which can increase tolerability and enable dose sparing.”
Recent advances and clinical prospects of non-viral brain-targeted gene delivery systems
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From Polymers to Nanomedicines: New Materials for Future Vaccines
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“Most studies regarding mRNA vaccines against RSV have been developed with mRNA encoding the native RSV F protein or the stabilized prefusion conformation delivered through cationic nanoemulsions and lipid nanoparticles [119,120].”
BackgroundSemliki Forest virus-based immunotherapy for cancer
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A Self-Assembled Non-Viral vector as Potential Platform for mRNA-Based Vaccines
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Orthoflavivirus Vaccine Platforms: Current Strategies and Challenges
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“Although saRNA constructs are larger than mRNA vaccines (9–11 kb), they have shown compatibility with nanoparticle delivery systems [199–201].”
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A Historical Overview on mRNA Vaccine Development
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Session 4: mRNA and Self-Amplifying RNA (saRNA): Opportunities for Disease Prevention and Therapy
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“16 saRNA is constructed by retaining the viral replication machinery (nonstructural proteins: nsp1-4) but replacing viral structural proteins with target antigen sequences under key regulatory elements.”
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“Except for a 5’ cap and a 3’ poly(A) tail, saRNA has a basic structure that contains four nonstructural genes NSP1–4, 26S subgenomic promoter, and the gene of interest [50].”
BackgroundApplication of self-amplifying mRNA technology in the development of infectious disease vaccines
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“This process might be similar to self-replicating mRNA vaccines but is potentially easier to achieve while retaining the influenza virus’s affinity for certain cells or tissues [31].”
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“Previous studies investigating temporal changes in proteins encoded by the mRNA of saRNA vaccines have reported that the disappearance of the protein occurs by 28 [12] or 63 [13] days after vaccination.”
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Respiratory Syncytial Virus Prevention in the Adult Population: State of the Art
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“Pre-clinical proof of principle has been achieved for multiple SAM vaccines, which could radically simplify the way rationally-designed vaccine antigens are discovered, developed and manufactured [4].”
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Vaccines: past, present and future
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Advancement in Nanomaterials for Rapid Sensing, Diagnosis, and Prevention of COVID-19
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Towards a Prophylactic Vaccine for the Prevention of HCMV Infection
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Hospital-Based RNA Therapeutics
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Learning from cancer to address COVID-19
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Technologies for Making New Vaccines
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Hospital-based RNA TherapeuticsPreprint
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“In vivo replicating RNA technologies have been under development for many years(Geall et al. 2012; Bogers et al. 2015).”
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Nanotechnology-based approaches against COVID-19
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Pathogenesis and Immunity of SARS-CoV-2 and Vaccination Programs Against COVID-19
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Sequence-Optimized mRNA Vaccines Against Infectious Disease
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Use of Nanotechnology in the Formulation of Vaccines
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Nanoparticles for mRNA-based cancer immunotherapy
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Harnessing mRNA vaccines for viral diseases: bottleneck and breakthrough
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Host Responses to SARS-CoV-2 with an Emphasis on Cytokines
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“To enhance cost-effectiveness and immunogenicity, self-amplifying RNA vaccines have been engineered using NSPs from equine viruses to enable intracellular replication of the RNA payload [120–123].”
Kunyk, D., Vasileva, O., Bespalov, M., Dzharullaeva, A. S., Mazunina, E., Chubarova, A., Seliverstov, M., Smirnykh, D., Shevyrev, D., Shtraus, S., et al. (2026) · ChemMedChem · doi:10.1002/cmdc.70335 · Cited by 2
Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering
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“Among available backbones, VEEV replicons have emerged as the dominant platform, owing to their pronounced lymphotropism, relatively low vector immunity, strong innate immune activation, and robust heterologous gene expression compared with Old World alphaviruses such as SINV or SFV (149).”
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“In 61–63 Tri-link prepared conventional mRNA with the same Rabies Virus Glycoprotein sequence, incorporating n-1-methyl-pseudouridine in place of uridine.”
InfluentialRecent progress in the rational design of mRNA vaccines
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mRNA Vaccine Review against COVID-19 with Potential Applications to Improve Efficacy and Targeting
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“However, limitations are that nucleotide sequences cannot handle much modification and so it is not versatile, the replicon size is very large to account for the two sections to aid in viral protein replication, and inclusion of potential unrelated protein responses due to the increased amount of replicon available in…”
MethodPerspective Chapter: Next-Generation Vaccines Based on Self-Amplifying RNA
Nafian, F., Nafian, S., Soleymani, G., Pourmanouchehri, Z., Kiyanjam, M., Jalaei, S. B., Jeyroudi, H., & Mohammdi, S. M. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.101467 · Cited by 2
Adjuvants, the Elephant in the Room for RNA Vaccines
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RNA therapeutics for infectious diseases
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Personalized vaccines, novel vaccination technologies, and future prospects
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Lipid nanoparticles loaded with anticancer bioactives: state of the art
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Entwicklung von RNA‐basierten Impfstoffen
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“der Vermehrung der mRNAs entsteht vorübergehend Doppelstrang-RNAs, die selbst immunstimulierend wirken [9].”
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Integrating Context of Tumor Biology and Vaccine Design to Shape Multidimensional Immunotherapies
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COVID-19 as milestone for the use of new vaccine types
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“On the other hand, self-amplifying mRNAs besides target antigen encode the proteins involved in viral replication, enabling their intracellular amplification [47].”
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“Healthy volunteers will receive a single dose of 5 × 105, 5 × 106, or 5 × 107 pfu of VSV∆G-SARS-CoV-2 (IIBR-100) for the evaluation of the safety, immunogenicity, and potential efficacy of the vaccine candidate.”
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Knudsen, M. (2014) · Figshare · Cited by 1
Current Status of Cytomegalovirus Vaccines: 2016
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Next-generation salmonid alphavirus vaccine development
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Metadata
- Authors
- Geall, A. J., Verma, A., Otten, G. R., Shaw, C. A., Hekele, A., Banerjee, K., Cu, Y., Beard, C. W., Brito, L. A., Krucker, T., O’Hagan, D. T., Singh, M., Mason, P. W., Valiante, N. M., Dormitzer, P. R., Barnett, S. W., Rappuoli, R., Ulmer, J. B., & Mandl, C. W.
- Affiliations
- Novartis Vaccines and Diagnostics, Cambridge, MA 02139; and
- Novartis Institutes for BioMedical Research, Cambridge MA 02139
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-08-20
- Volume
- 109
- Issue
- 36
- Pages
- 14604-14609
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3437863
- OpenAlex
- W2051665875
- Cited by
- 675
- References
- 41
- Citations by year
- 2026: 34 · 2025: 63 · 2024: 66 · 2023: 66 · 2022: 79 · 2021: 78 · 2020: 74 · 2019: 41 · 2018: 31 · 2017: 28 · 2016: 31 · 2015: 27 · 2014: 31 · 2013: 24 · 2012: 2
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (5P01 AI066287, P01AI066287)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- self-amplifying RNA vaccine, lipid nanoparticles, siRNA delivery, nucleic acid vaccines, immunogenicity, protective immune response
- MeSH terms
- Alphavirus, Analysis of Variance, Animals, Electrophoresis, Agar Gel, Escherichia coli, Female, Fluorescent Antibody Technique, Humans, Lipids, Drug Delivery Systems, Statistics, Nonparametric, Vaccines, DNA, RNA, Small Interfering, Rats, Nanoparticles
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